Nuclear factor-kappa B1 controls the functional maturation of dendritic cells and prevents the activation of autoreactive T cells

作者：Dissanayake Dilan; Hall Hakan; Berg Brown Nancy; Elford Alisha R; Hamilton Sara R; Murakami Kiichi; Deluca Leslie Summers; Gommerman Jennifer L; Ohashi Pamela S^*

来源：Nature Medicine, 2011, 17(12): 1663-U182.

DOI：10.1038/nm.2556

Mature dendritic cells (DCs) are crucial for the induction of adaptive immune responses and perturbed DC homeostasis can result in autoimmune disease. Either uncontrolled expansion(1) or enhanced survival(2,3) of DCs can result in a variety of autoimmune diseases in mouse models. In addition, increased maturation signals, through overexpression of surface Toll-like receptors (TLRs)(4) or stimulation by type I interferon (IFN)(5), has been associated with systemic autoimmunity. Whereas recent studies have focused on identifying factors required for initiating the maturation process, the possibility that resting DCs also express molecules that 'hold' them in an immature state has generally not been considered. Here we show that nuclear factor-kappa B1 (NF-kappa B1) is crucial for maintaining the resting state of DCs. Self-antigen-pulsed unstimulated DCs that do not express NF-kappa B1 were able to activate CD8(+) T lymphocytes and induce autoimmunity. We further show that NF-kappa B1 negatively regulates the spontaneous production of tumor necrosis factor-alpha (TNF-alpha), which is associated with increased granzyme B expression in cytotoxic T lymphocytes (CTLs). These findings provide a new perspective on functional DC maturation and a potential mechanism that may account for pathologic T cell activation.

• 出版日期2011-12